Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

ObjectiveTo conduct a meta-analysis of the prevalent characteristics of the injury-related behaviors among adolescents in China based on Chinese literature, so as to inform the prevention and control of injury-related behaviors of this population. MethodsA cross-sectional study on the prevalent characteristics of adolescent injury-related behaviors was conducted with the data collected from CNKI, VIP, Wanfang Data, CBM, PubMed, and Web of Science. The review included publications from the inception of the databases to November 2023. Meta-analysis was performed with Stata 15.1 software. ResultsA total of 40 articles were included in this study, and the meta-analysis results showed that cycling violation rate was 38% (95%CI: 32%‒43%), walking violation rate was 29% (95%CI: 22%‒36%), rate of unsafe swimming was 13% (95%CI: 11%‒14%), suicidal ideation rate was 13% (95%CI: 12%‒15%) and the prevalence of fighting was 19% (95%CI: 17%‒22%). Subgroup analysis showed that the cycling violation rate was (44%) for boys and 34% (95%CI: 28%‒40%) for girls. Adolescents in Northeast, East, and Southwest of China had the highest rate of cycling violation (44%), of which junior high school students had the highest rate of violation [42% (95%CI: 36%‒49%)]. As for the walking violation rate, male students [29% (95%CI: 21%‒37%)] was higher than that of female students [22% (95%CI: 15%‒30%)]. Adolescents in North of China had the highest rate of walking violation [54% (95%CI: 30%‒76%)], of which vocational school students accounted for 38% (95%CI:21%‒56%) of the total violation. In terms of the detection rate of unsafe swimming, male students [18% (95%CI: 14%‒24%)] was higher than that of female students [8% (95%CI: 6%‒10%)]. Adolescents in Central South China had the highest rate of unsafe swimming [15% (95%CI: 12%‒18%)], of which, vocational school students accounted for the highest [15% (95%CI: 10%‒19%)]. When it comes to the prevalence of suicidal ideation, female students [16% (95%CI: 13%‒19%)] was higher than that of male students [13% (95%CI: 11%‒15%)]. Adolescents in Southwest of China had the highest rate of suicidal ideation [17% (95%CI: 10%‒25%)], of which high school students accounted for the highest [15% (95%CI: 12%‒18%)]. Finally, the detection rate of fights was 30% (95%CI: 26%‒34%) for boys and 11% (95%CI: 10%‒14%) for girls. Adolescents from Southwest of China had the highest rate [29% (95%CI: 24%‒34%)] for fights, and junior high school students accounted for the highest [26% (95%CI: 22%‒31%)]. ConclusionThe prevalence of harmful behaviors among adolescents in China is notably high, with statistical differences across gender, region, and school stages. These behaviors pose a risk to adolescent health, underscoring the need for targeted interventions by health and educational authorities.

The standardized workflow of computer-aided static guided implant surgery includes preoperative exami-nation,data acquisition,guide design,guide fabrication and surgery.Errors may occur at each step,leading to irrevers-ible cumulative effects and thus impacting the accuracy of implant placement.However,clinicians tend to focus on fac-tors causing errors in surgical operations,ignoring the possibility of irreversible errors in nonstandard guided surgery.Based on the clinical practice of domestic experts and research progress at home and abroad,this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection,data collection,guide de-signing and manufacturing and describes strategies to resolve errors so as to gain expert consensus.Consensus recom-mendation:1.Preoperative considerations:the appropriate implant guide type should be selected according to the pa-tient's oral condition before surgery,and a retaining screw-assisted support guide should be selected if necessary.2.Da-ta acquisition should be standardized as much as possible,including beam CT and extraoral scanning.CBCT performed with the patient's head fixed and with a small field of view is recommended.For patients with metal prostheses inside the mouth,a registration marker guide should be used,and the ambient temperature and light of the external oral scan-ner should be reasonably controlled.3.Optimization of computer-aided design:it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers.Properly designing the retaining screws,extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors.4.Improving computer-aided production:it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postpro-cessing procedures.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

Humans ; Microglia ; Spinal Cord ; Neuralgia ; Hyperalgesia

Objective:To integrate the best evidence of non-drug intervention of urinary incontinence in elderly women and to formulate practical recommendations.Methods:In this systematic review study, using “elderly woman”,“urinary incontinence”,“bladder training”,“pelvic floor muscle training”,“enuresis”,“leakage of urine” as the key words, the 6S evidence resource pyramid model was used to search in British Medical Journal best practice, Uptodate, World Health Organization, Guidelines International Network, National Institute for Health and Care Excellence, Chinese Medical Association, Scottish Intercollegiate Guideline Network, Registered Nurses Association of Ontario, Cochrane Library, The Joanna Briggs Institute (JBI), New Zealand Guidelines Group, Polish Society of Gynecologists and Obstetricians, PubMed, Embase, Medline, Web of Science, SinoMed, China National Knowledge Infrastructure, WanFang Data, etc. The evidence retrieved included evidence-based knowledge base resources, clinical practice guidelines, expert consensus, systematic review, etc. Data were retrieved from January 1, 2017 to May 1, 2022, and collated from May 2, 2022 to May 25, 2022. Two researchers independently evaluated the quality of literature and extracted data using the AGREE Ⅱ and JBI evidence-based health care center assessment tools. The JBI evidence-based health care center′s evidence pre-rating system and evidence recommendation rating system were applied to rank the evidence; and under the guidance of the evidence structure of JBI, the strength of evidence recommendation was determined and the best evidence was extracted and summarized in combination with the study group discussion and expert opinion.Results:A total of 9 articles were retrieved, including 7 guidelines and 2 systematic reviews; and 6 guidelines were classified as Grade A and 1 as grade B; both 2 systematic reviews were rated as Grade A; 84% (27/32) of the items were evaluated as “Yes”. Evidence were summarized as 34 pieces of best evidence from 6 dimensions, including “overall recommendation, evaluation of type and degree of urinary incontinence, lifestyle change, behavioral therapy, prevention of precipitating factors, intervention in special population”; the flow chart of screening, evaluation, special symptoms, life style and behavior therapy was combed, and the practical suggestions were formed.Conclusions:The overall quality of the literature on non-drug intervention of urinary incontinence in elderly women is high, and the level of evidence is high. Early identification of urinary incontinence types and assessment of disease severity, lifestyle changes, avoidance of predisposing factors and behavioral therapy are the key to non-drug treatment of urinary incontinence in those patients.

OBJECTIVES: To study the correlation of intestinal dominant flora with hyperuricemia, and to explore influencing factors of hyperuricemia. METHODS: Data of gut dominant microbiota were collected from subjects who underwent health check-up in Shulan (Hangzhou) Hospital from January 2018 to April 2020. Subjects with high uric acid and normal uric acid were matched by propensity score matching method according to age, gender and body mass index (BMI). This resulted in 178 pairs as hyperuricemia group and control group. The gut dominant microbiota between hyperuricemia and normal control group were compared. Pearson or Spearman correlation coefficient method was used to analyze the correlation between blood uric acid and intestinal dominant flora. Univariate and multivariate logistic regression were used to analyze the influencing factors of hyperuricemia. RESULTS: The abundance of Atopobium, Lactobacillus, Bacteroides, Enterococcus, Clostridium leptum, Fusobacterium prausnitzii, Bifidobacterium, Clostridium butyricum and the ratio of Bifidobacterium to Enterobacter (B/E) in the hyperuricemia group were significantly lower than those in the control group (all P<0.01). The correlation analysis showed that serum uric acid were negatively correlated with the abundance of Atopobium (r=－0.224, P<0.01), Bacteroides (r=－0.116, P<0.05), Clostridium leptum (r=－0.196, P<0.01), Fusobacterium prausnitzii (r=－0.244, P<0.01), Bifidobacterium (r=－0.237, P<0.01), Eubacterium rectale (r=－0.125, P<0.05), Clostridium butyricum (r=－0.176, P<0.01) and B/E value (r=－0.127, P<0.05). Multivariate logistic regression analysis showed that glutamyl transpeptidase was an independent risk factor for hyperuricemia (OR=1.007, 95%CI: 1.002-1.012, P<0.05), and the Atopobium was an independent protective factor for hyperuricemia (OR=0.714, 95%CI: 0.605-0.842, P<0.01). CONCLUSIONS There are alterations in abundance of gut dominant microbiota in patients with hyperuricemia, and Atopobium abundance appears as a protective factor for hyperuricemia.
Humans ; Uric Acid ; Hyperuricemia ; Body Mass Index ; Risk Factors ; Microbiota

Objective To improve the clinical recognition of anti-leucine-rich glioma inactivated-1(LGI1)antibody associated encephalitis through investigating the clinical characteristics of the disease,so as to improve diagnosis and prognosis.Methods A total of 31 consecutive patients with anti-LGI1 antibody associated encephalitis were recruited during January 2020 to March 2022 in Brain Hospital Affiliated to Nanjing Medical University including their clinical manifestations.Patients were divided into first-line immunotherapy group and mycophenolate mofetil(MMF)adding-on group according to the initial treatment regimen.Univariate and multivariate COX regression analysis were used to analyze the factors of the recurrence of anti-LGI1 antibody encephalitis.mRS was used to evaluate the prognosis.Results Seizure(93.5%),memory defect(80.6%)and psychosis(58.1%)were the most common manifestations in 31 patients.Fourteen patients suffered with hyponatremia,1 patients with elevated white cells and 17 patients with elevated proteins in CSF.The corresponding positive rates of anti-LGI1 antibody were 90.3%and 93.1%in serum and CSF.Fourteen patients had abnormal cranial MR.All patients received first-line immunotherapy,with 13 patients followed by MMF.Eleven patients were recurred in the follow-up.Univariate COX regression analysis found female(HR =3.85,95%CI:1.12-13.24,P =0.032),MMF adding-on therapy(HR = 4.03,95%CI:1.07-15.22,P = 0.04)were associated with relapse.However no independent associations were found after multivariate COX regression analysis.Twenty-two patients had sequeleas during follow-up,with memory decline as the most common symptom.All patients achieved good prognosis.Conclusions Anti-LGI1 antibody associated encephalitis may have good prognosis,but relapse is not rare.The majority patients have sequelaes,with memory defect and psychosis being the most common symptoms.MMF might have no prevention effect on anti-LGI1 antibody encephalitis recurrence.

Objectives:the purpose of this study was to systematically evaluate the clinical value of cytokines in autoimmune diseases (AID). It was a kind of complex disease, and its pathogenesis involved cytokines, autoantibodies, immune cells and other immune factors. Especially some AID, such as Adult still′s disease (AOSD) and Takayasu arteritis(TA), had no specific biomarkers at present. This study was a retrospective case-control study.Methods:the data of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) in 834 AID patients from January 2019 to August 2022 were collected, and the serum levels of those cytokines in 30 healthy controls (HC) were detected at the same time. And AOSD, TA, systemic lupus erythematosus (SLE) and Behcet′s syndrome (BS) were divided into active group and inactive group. In addition, we also made a subgroup analysis of two important organs involved in SLE (kidney and nervous system). GraphPad Prism 9 and R 4.2.2 software were used. Nonparametric tests (Kruskal-Wallis H test, Mann-Whitney U test) were used to compare the differences among groups, and Dunn′s method was used to correct the false positive caused by multiple tests. Results:To compare the level of IL-6 in each group, except Behcet syndrome (BS) group and antiphospholipid syndrome (APS) group, the serum IL-6 level of AID group was higher than that of HC group, with antineutrophil cytoplasmic antibodies associated vasculitis(AAV) [3.85(2.00,8.55) pg/ml], idiopathic inflammatory myopathies(IIM) [7.80(2.50,6.50)pg/ml], IgG4-related disease(IgG4RD) [3.65(2.08,12.83) pg/ml], rheumatoid arthritis (RA) [5.50(2.20,16.10) pg/ml], SLE[4.70(2.75,16.55) pg/ml], Sj?gren syndrome(SS) [3.20(2.00,8.90) pg/ml], systemic sclerosis(SSc) [2.70(2.00,8.90) pg/ml], TA[3.40 (2.00,6.50) pg/ml], other AID diseases[4.40(2.00,11.10) pg/ml], especially AOSD [15.20(2.10, 39.20) pg/ml]. After correction, the differences were statistically significant ( P c<0.05). At the same time, the levels of serum TNF-α [7.40(5.60,10.95) pg/ml]and IL-10 [5.00(5.00, 7.58) pg/ml] in AOSD group were significantly higher than those in HC group[7.15(5.93,8.00) pg/ml,5.00(5.00,5.00) pg/ml] after correction ( P c<0.05). At the same time, the levels of serum TNF-α and IL-10 in AOSD group were higher than those in HC group. The serum levels of IL-6 and IL-8 in patients with active AOSD, BS, SLE and TA were significantly higher than those in patients without active disease (all P<0.05). In addition, the level of serum IL-8 in lupus nephritis group was significantly higher than that in non-lupus nephritis group ( P<0.05). At the same time, the serum levels of IL-6, IL-8 and TNF-α in neuropsychiatric lupus erythematosus group were significantly higher than those in non-neuropsychiatric lupus erythematosus group ( P<0.05), but there was no significant difference in IL-10 between neuropsychiatric lupus group and non-neuropsychiatric lupus erythematosus group. Conclusions:there was a close relationship between AID and cytokines. At present, the change of serum IL-6 level was the most classic one in clinical routine.